NMR spectroscopy represents the most powerful technique currently available for examining conformational changes in protein structure induced by small molecules in solution. The technique can also provide important information on the identification of the specific amino acid residues within the protein that are involved in the binding reaction, the orientation of the small molecule at the binding site, and the effect of the interaction on the overall conformation of the protein. The high resolution of NMR makes it a particularly suitable technique for investigation of protein-lipid interactions. This proposal outlines a series of experiments designed to ascertain the nature of the interactions with and the binding sites on the myelin basic protein of some myelin specific lipids and a variety of model compounds. The studies proposed will fall into four general categories. The first group of experiments will deal with an examination of external conditions (e.g., pH, ionic strength, etc.) on the structure of the basic protein in aqueous conditions in the absence of ligands. The second group of experiments will deal with chemical modifications of the protein and the absolute assignment of specific resonances within the NMR spectrum. The third group of experiments will deal with the binding of selected ligands to both modified and unmodified myelin basic proteins. The last series of experiments will be devoted to measurements of both the protein and lipid NMR spectra in phospholipid vesicles containing the myelin basic protein. Such studies should provide concrete information about conformational changes induced in the protein by the ligands, the orientation of the ligand with respect to the protein, and the specific residues on the protein involved in the binding of the ligand, both when the protein is free in solution and when it is part of a membrane.